The present invention relates to a new salt of an azo derivative of 5-aminosalicylic acid, and more particularly to the sodium salt of (Z)-2-hydroxy-5-[[4-[3-[4-[(2-methyl-1H-imidazo[4,5-c ]pyridin-1-yl)methyl]-1-piperidinyl]-3-oxo-1-phenyl-1-propenyl]phenyl]azo]benzoic acid. The present invention also relates to the pharmaceutical compositions containing it, to a procedure for its preparation and to its use for the manufacture of medicaments useful for the treatment or prevention of inflammatory bowel disease.
Inflammatory bowel disease is a chronic inflammatory disease of the intestine, whose etiology is still unknown. The most prevalent forms of this disease are ulcerative colitis and Crohn""s disease.
Patent application WO 97/09329 discloses a series of azo derivatives of 5- aminosalicylic acid (5-ASA) that are useful for the treatment of inflammatory bowel disease. These compounds combine in the same molecule 5-ASA and a compound having PAF-antagonist activity through an azo bond, and are designed to be metabolized in the colon by the intestinal bacteria in a similar manner to that described for the reference compound sulfasalazine, to deliver 5-ASA and the PAF antagonist. One of the compounds described in this patent application is (Z)-2-hydroxy-5-[[4-[3-[4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinyl]-3-oxo-1-phenyl-1-propenyl]phenyl]azo]benzoic acid, which is known in the literature as UR-12746 and whose formula is shown below: 
The authors of the present invention have found that the levels of azoreduction observed with this compound are low when studies on the metabolization of said azo bond are carried out. Since this kind of compounds are precisely designed to be metabolized and deliver in the colon 5ASA and the PAF antagonist, which are the active molecules, the problem arises of finding compounds that are metabolized in the colon to a greater extent. This problem is solved with the new salt that is the object of the present invention.
The present invention relates to the sodium salt of (Z)-2-hydroxy-5-[[4-[3-[4-[(2-methyl-1H-imidazo[4,5-c ]pyridin-1-yl)methyl]-1-piperidinyl]-3-oxo-1-phenyl-1-propenyl]phenyl]azo]benzoic acid of formula I: 
It has been found that the sodium salt of the invention (i.e. the sodium salt of UR-12746) can exist in different forms, in particular in amorphous or noncrystalline form and in crystalline form. It has further been found that the sodium salt of the invention exists in two different crystalline forms, designated polymorph I and polymorph II, depending on the preparation conditions, as explained in greater detail below. The present invention relates to the sodium salt of UR-12746 in any of its forms.
The present invention also relates to a process for the preparation of the sodium salt of formula I.
The present invention further relates to a pharmaceutical composition which comprises an effective amount of the sodium salt of formula I and one or more pharmaceutically acceptable excipients.
The present invention also relates to the use of the sodium salt of formula I for the manufacture of a medicament for the treatment or prevention of inflammatory bowel disease. Throughout the present description, the term xe2x80x9cinflammatory bowel diseasexe2x80x9d is to be understood as comprising ulcerative colitis, Crohn""s disease as well as any other form of inflammatory bowel disease.